We have previously disclosed 2-substituted-4-heteroaryl-pyrimidines and their use in the treatment of proliferative disorders (Fischer P M, Wang S. PCT Intl. Patent Appl. Publ. WO 01/072745; Cyclacel Limited, UK, 2001). These compounds inhibit cyclin-dependent protein kinases (CDKs), in particular CDK4/cyclin D, CDK2/cyclin E, CDK2/cyclin A, and CDK1/cyclin B, i.e. enzyme complexes that are important in human cell cycle progression. Furthermore, 2-phenylamino-4-heteroaryl-pyrimidines possess selective in vitro and in vivo antiproliferative activity against a range of human tumour cells (Wang S, Blake D, Clarke R, Duff S, McClue S J, McInnes C, Melville J, Stewart K, Taylor P, Westwood R, Wood G, Wu S-Y, Zhelev N Z, Zheleva D I, Walkinshaw M, Lane D P, Fischer P M. Proc. Amer. Assoc. Cancer Res. 2002; 43: 4202).
The present invention seeks to provide further 2-substituted-4-heteroaryl-pyrimidines. More specifically, the present invention preferably seeks to provide 2-substituted-4-heteroaryl-pyrimidines which display improved aqueous solubility and/or bioavailability.